Caprine arthritis-encephalitis virus (CAEV) is a persistent lentiviral pathogen of goats, associated with disease of a variety of organ systems, including brain, lung, mammary gland and synovium. The principle target of infection is the macrophage, with proviral integration in this cell type. However viral transcripts have also been found in intestinal epithelium. Disease occurs in the presence of anti-gp135 envelope glycoprotein antibodies, which are incapable of neutralizing viral infectivity. The major route of infection by CAEV appears to be ingestion of colostrum and milk from infected dams, although horizontal spread can occur later in life. Despite this relatively restricted means of initiating infection, virtually nothing is known about events occurring during this process, about the pathologic lesions that result from infection, or about host- viral interactions at that site. The overall goal of the proposed research is to examine the pathogenesis of CAEV infection in the neonatal gut, using long-term xenografts implanted into nude mice. The first objective is to examine similarities and differences between caprine xenografts and uninfected maturing goat intestine, including the morphology, enzymatic complement, leukocytic constituents and ability to absorb colostral antibody, during a 3-4 week period after grafts are established. The second objective is determine the course of CAEV infection in grafts of various regions of intestine over a 3 week period, determining which cells are infected by virus, whether virus is released into the intestinal lumen, what pathologic lesions result from infection, and whether significant cytokine release results from infection. The third objective is to examine the ability of neutralizing and nonneutralizing antibodies to modify infection in xenografts. The fourth objective is to infect the intestine of Caprine neonates for analogous intervals to determine the usefulness of xenografts in simulating spontaneous infection and to determine early extraintestinal sites of viral replication. CAEV is likely to share several aspects of its pathogenesis with human lentiviruses HIV and HTLV, which are transmitted through milk and are partially trophic for macrophages. It is hoped that a greater understanding of the comparative pathogenesis of enteric infection by lentiviruses might suggest methods to circumvent infection or alter the severity of intestinal disease.